% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Liu:275263,
author = {Y. Liu and J. Klein and R. Bajpai and L. Dong and Q. Tran
and P. Kolekar and J. L. Smith and R. E. Ries and B. J.
Huang and Y.-C. Wang and T. A. Alonzo and L. Tian and H. L.
Mulder and T. I. Shaw and J. Ma and M. P. Walsh and G. Song
and T. Westover and R. J. Autry$^*$ and A. M. Gout and D. A.
Wheeler and S. Wan and G. Wu and J. J. Yang and W. E. Evans
and M. Loh and J. Easton and J. Zhang and J. M. Klco and S.
Meshinchi and P. A. Brown and S. M. Pruett-Miller and X. Ma},
title = {{E}tiology of oncogenic fusions in 5,190 childhood cancers
and its clinical and therapeutic implication.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-00710},
pages = {1739},
year = {2023},
abstract = {Oncogenic fusions formed through chromosomal rearrangements
are hallmarks of childhood cancer that define cancer
subtype, predict outcome, persist through treatment, and can
be ideal therapeutic targets. However, mechanistic
understanding of the etiology of oncogenic fusions remains
elusive. Here we report a comprehensive detection of 272
oncogenic fusion gene pairs by using tumor transcriptome
sequencing data from 5190 childhood cancer patients. We
identify diverse factors, including translation frame,
protein domain, splicing, and gene length, that shape the
formation of oncogenic fusions. Our mathematical modeling
reveals a strong link between differential selection
pressure and clinical outcome in CBFB-MYH11. We discover 4
oncogenic fusions, including RUNX1-RUNX1T1, TCF3-PBX1,
CBFA2T3-GLIS2, and KMT2A-AFDN, with promoter-hijacking-like
features that may offer alternative strategies for
therapeutic targeting. We uncover extensive alternative
splicing in oncogenic fusions including KMT2A-MLLT3,
KMT2A-MLLT10, C11orf95-RELA, NUP98-NSD1, KMT2A-AFDN and
ETV6-RUNX1. We discover neo splice sites in 18 oncogenic
fusion gene pairs and demonstrate that such splice sites
confer therapeutic vulnerability for etiology-based genome
editing. Our study reveals general principles on the
etiology of oncogenic fusions in childhood cancer and
suggests profound clinical implications including
etiology-based risk stratification and genome-editing-based
therapeutics.},
cin = {B062},
ddc = {500},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37019972},
doi = {10.1038/s41467-023-37438-4},
url = {https://inrepo02.dkfz.de/record/275263},
}